Visualization of secretory cargo transport within the Golgi apparatus

To describe trafficking of secretory cargo within the Golgi apparatus, the cisternal maturation model predicts that Golgi cisternae change their properties from cis to trans while cargo remains in the cisternae. Cisternal change has been demonstrated in living yeast Saccharomyces cerevisiae; however, the behavior of cargo has yet to be examined directly. In this study, we conducted simultaneous three-color and four-dimensional visualization of secretory transmembrane cargo together with early and late Golgi resident proteins. We show that cargo stays in a Golgi cisterna during maturation from cis-Golgi to trans-Golgi and further to the trans-Golgi network (TGN), which involves dynamic mixing and segregation of two zones of the earlier and later Golgi resident proteins. The location of cargo changes from the early to the late zone within the cisterna during the progression of maturation. In addition, cargo shows an interesting behavior during the maturation to the TGN. After most cargo has reached the TGN zone, a small amount of cargo frequently reappears in the earlier zone

Possible impact of ADRB3 Trp64Arg polymorphism on BMI in patients with schizophrenia

Background: The beta 3-adrenoceptor (ADRB3) gene Trp64Arg polymorphism has been shown to be associated with obesity as well as type 2 diabetes and cardiovascular disease. The incidence of overweight and the risks of type 2 diabetes and cardiovascular disease are also increased in major depression and schizophrenia. We hypothesized that the Trp64Arg polymorphism may be associated with increased risk of schizophrenia and depression. Methods: The Trp64Arg was genotyped in 504 patients with schizophrenia, 650 with major depressive disorder (MOD), and 1170 healthy controls. Of these participants, body mass index (BMI) data were available for 125 patients with schizophrenia, 219 with MDD, and 261 controls. Results: No significant difference in genotype or allele distribution was found across the diagnostic groups. No significant difference in BMI was observed between the Arg allele carriers and the non-carriers in the MDD and the control groups. However, patients with schizophrenia carrying the Arg allele had significantly higher BMI (Mean (SD): Arg carriers: 26.5 (6.9), Arg non-carriers: 23.8 (4.3); P=0.019) and a higher rate of being overweight (BMI of 25 or more) compared to their counterparts (Trp/Trp group) (% overweight (SE): Arg carriers: 52.3 (7.5), Arg non-carriers: 32.1 (5.2); P=0.027). Conclusions: We obtained no evidence for the association of ADRB3 Trp64Arg with the development of MDD or schizophrenia. However, the Arg allele was found to be associated with higher BMI and being overweight in patients with schizophrenia. This may imply that genotyping ADRB3 is of clinical use to detect schizophrenic individuals at risk for developing obesity.ArticlePROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY. 38(2):341-344 (2012)journal articl

Cross-talk between TLR3 and TNF-α or IFN-γ Signaling in Induction of CXCL8/IL-8 and CXCL10/IP-10 Expression in Airway Epithelial Cells

CXCL8/IL-8 is a chemoattractant for neutrophils and mast cells, and regulates inflammatory cell recruitment in allergy, infection, and other neutrophil-related diseases. Interferon (IFN) -γ-inducible protein 10 (CXCL10/IP-10) is a chemokine that attracts mononuclear cells, Th1 cells, and natural killer cells. We investigated the levels of CXCL8/IL-8 and CXCL10/IP-10 expression by airway epithelial cells after exposure to the inflammatory cytokines tumor necrosis factor (TNF) -α and IFN-γ, and to poly I:C, a synthetic analog of double-stranded RNA that is a ligand of Toll-like receptor 3 (TLR3). Poly I:C, TNF-α, IFN-γ, and combinations of poly I:C with TNF-α or IFN-γ were used to stimulate the airway epithelial cell line BEAS-2B. Following stimulation, we determined CXCL8/IL-8 and CXCL10/IP-10 mRNA levels by real-time PCR and protein levels by ELISA. Poly I:C treatment upregulated mRNA and protein expression for both CXCL8/IL-8 and CXCL10/IP-10. The addition of TNF-α, but not IFN-γ, to poly I:C further increased the expression of CXCL8/IL-8 mRNA and protein. The addition of either TNF-α or IFN-γ to the poly I:C treatment further increased CXCL10/IP-10 mRNA and protein expression. Cross-talk between TLR3 signaling and inflammatory cytokines regulates the expression of CXCL8/IL-8 and CXCL10/IP-10 in airway epithelial cells. From our results, TNF-α and IFN-γ produce different effects on TLR3 signaling

Kakaisho owned by Doshisha Women\u27s College of Liberal Arts : the text with an introduction (1)

　『河海抄』は貞観元年 (1362年) 頃に四辻善成によって作られた『源氏物語』の注釈書であり、源氏学初期の集大成で、以後の注釈の規範的位置を示すものである。『河海抄』執筆の基本的姿勢は『源氏物語』を歴史の中に置き、いかにその文章や構想が歴史的事実に依拠したものであるかを詳細に説明している。特に、本報告で扱った「料簡」はその性格が強く、「いづれの御時にか」で繙かれる『源氏物語』の虚構世界を「醍醐・朱雀・村上天皇」の三代の御代に設定し、主人公光源氏の解釈も実在の歴史上の人物に依ることで、新たな『源氏物語』の読みを展開している。こういった視点は原典をより深く読むための手掛かりとなる。　そこで、本稿では同志社女子大学図書館蔵本を底本として、演習に参加した大学院生を中心に『河海抄』の翻刻と注釈を行った。今回の報告ではその中の「序」と「料簡」を掲載する

Priority stratification for colonoscopy based on two-sample faecal immunochemical test screening: results from a cross-sectional study at an endoscopy clinic in Japan

Objectives Little has been reported on the yield and characteristics of colorectal neoplasia detected by the two-sample faecal immunochemical test (FIT), particularly the difference between subjects with two-positive results on the two-sample FIT and those with one-positive results. We aimed to assess risk stratification among patients with positive two-sample FIT to prioritise colonoscopy.Design A retrospective cross-sectional study.Setting A single-centre, representative endoscopy clinic in Japan.Participants Consecutive patients who underwent colonoscopy were enrolled. Indications for colonoscopy included two-positive results on the two-sample FIT (FIT (+/+)), one-positive results on the two-sample FIT (FIT (+/−)), and other reasons (non-FIT group, including presence of symptoms, screening or surveillance).Primary and secondary outcome measures Primary outcomes were detection rates of colorectal cancers, including in situ (all cancers) and invasive cancers, based on the indications for colonoscopy. Secondary outcomes were cancer features, such as location, size, T stage and histological subtype.Results Of the 8724 patients, 264 underwent colonoscopy following FIT (+/+), 1018 following FIT (+/−) and 7442 for reasons other than positive FIT. Detection rates of all (and invasive) cancers in the FIT (+/+), FIT (+/−) and non-FIT groups were 12.1% (8.3%), 1.9% (0.3%) and 0.4% (0.2%), respectively. The cancer detection rates were much higher in the FIT (+/+) group than in the FIT (+/−) group, which in turn had higher rates than the non-FIT group. Moreover, the FIT (+/+) group showed more advanced T stages on tumour, node, metastasis (TNM) classification (Tis/T1/T2/T3/T4: 10/7/4/10/1) than the FIT (+/−) group (16/1/2/0/0, p<0.001).Conclusions Two-positive results for two-sample FIT showed a much higher yield for more advanced colorectal cancers than the one-positive result. High priority for diagnostic colonoscopy should be assigned to patients with two-positive-FIT results

DNA Origami Nanoplate-Based Emulsion with Designed Nanopore Function

Bio-inspired functional microcapsules stabilised with surfactants, copolymers, and nano/microparticles have attracted much attention in many fields from physical/chemical science to artificial cell engineering. Although the particle-stabilized microcapsules have advantages for their stability and rich ways for functionalisation such as surface chemical modifications and shape control of particles, versatile methods for their designable functionalisation are desired to expand their possibilities. Here, we report a DNA-based microcapsule composed of a water-in-oil microdroplet stabilised with amphiphilised DNA origami nanoplates. By utilising function programmability achieved by DNA nanotechnology, the DNA nanoplates were designed as a nanopore device for ion transportation as well as the interface stabiliser. Microscopic observations showed that the microcapsule formed by amphiphilic DNA nanoplates accumulated at the oil-water interface. Ion current measurements demonstrated that pores in the nanoplates functioned as ion channels. These findings provide a general strategy for programmable designing of microcapsules for engineering artificial cells and molecular robots.<br /

ADAMTSL6β Protein Rescues Fibrillin-1 Microfibril Disorder in a Marfan Syndrome Mouse Model through the Promotion of Fibrillin-1 Assembly

This research was originally published in the Journal of Biological Chemistry. Masahiro Saito, Misaki Kurokawa, Masahito Oda, Masamitsu Oshima, Ko Tsutsui, Kazutaka Kosaka, Kazuhisa Nakao, Miho Ogawa, Ri-ichiroh Manabe, Naoto Suda, Ganburged Ganjargal, Yasunobu Hada, Toshihide Noguchi, Toshio Teranaka, Kiyotoshi Sekiguchi, Toshiyuki Yoneda and Takashi Tsuji. ADAMTSL6β Protein Rescues Fibrillin-1 Microfibril Disorder in a Marfan Syndrome Mouse Model through the Promotion of Fibrillin-1 Assembly. J. Biol. Chem. 2011; 286: 38602-38613 © the American Society for Biochemistry and Molecular Biolog